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Background <p><i>Zataria multiflora</i> (ZM) is a medicinal plant with widespread antitumor effects. Tyrosine kinase inhibitors (TKIs) are considered the mainstay treatment in blood cancers; however, eventual resistance to TKIs poses a significant challenge in this area. The present study aimed to assess the synergistic effects of ZM extract (ZME) along with imatinib, a TKI, against K-562 and U-266 leukemic cell lines.</p> Methods <p>Cell viability was evaluated using the MTT assay, and apoptosis assessment was also conducted through Annexin-V/PI staining. Additionally, Real-Time PCR was used to assess the expression levels of <i>BCR-ABL</i>, <i>P-TEN</i>, <i>c-MYC</i>, <i>Bax</i>, and <i>Bcl-2</i> genes. Molecular docking was carried out as an in-silico technique for both BCL-2 and ABL proteins.</p> Results <p>The results showed that both ZME and imatinib promoted apoptosis in K562 and U266 cells, with combination treatment significantly enhancing apoptotic cell death (e.g., 18.4% apoptosis in K562 cells with ZME + imatinib vs. 8.5% untreated; 46.9% in U266 cells vs. 11.6% untreated, <i>P</i> &lt; 0.05). Combined treatment with imatinib and ZME upregulated the expression of <i>Bax</i> (5-fold in K562, 3-fold in U266) and <i>P-TEN</i> (2-fold in K562, 2.8-fold in U266) genes and downregulated the expression of <i>Bcl-2</i> (0.3-fold in K562, 0.3-fold in U266), <i>BCR-ABL</i> (0.5-fold in K562), and <i>c-MYC</i> (0.4-fold in K562, 0.2-fold in U266) genes (<i>P</i> &lt; 0.05). Molecular docking showed strong binding affinities between ZME constituents (carvacrol and thymol) and BCL-2 and ABL proteins.</p> Conclusions <p>ZME shows potential as a complementary agent in vitro, warranting further investigation.</p>

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Zataria multiflora extract enhances imatinib-induced cytotoxicity in chronic myeloid leukemia and multiple myeloma cells

  • 期刊论文

  • 发表日期：

    2025年10月14日

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  • Sahar Mostajeran,
  • Mohsen Ehsan,
  • Mahla Lashkari,
  • Hajar Mardani Valandani,
  • Ahmad Fatemi,
  • Ali Bazi,
  • Mahdieh Mirzaie,
  • Muhammad Hossein Ashoub,
  • Roohollah Mirzaee Khalilabadi

摘要

Background

Zataria multiflora (ZM) is a medicinal plant with widespread antitumor effects. Tyrosine kinase inhibitors (TKIs) are considered the mainstay treatment in blood cancers; however, eventual resistance to TKIs poses a significant challenge in this area. The present study aimed to assess the synergistic effects of ZM extract (ZME) along with imatinib, a TKI, against K-562 and U-266 leukemic cell lines.

Methods

Cell viability was evaluated using the MTT assay, and apoptosis assessment was also conducted through Annexin-V/PI staining. Additionally, Real-Time PCR was used to assess the expression levels of BCR-ABL, P-TEN, c-MYC, Bax, and Bcl-2 genes. Molecular docking was carried out as an in-silico technique for both BCL-2 and ABL proteins.

Results

The results showed that both ZME and imatinib promoted apoptosis in K562 and U266 cells, with combination treatment significantly enhancing apoptotic cell death (e.g., 18.4% apoptosis in K562 cells with ZME + imatinib vs. 8.5% untreated; 46.9% in U266 cells vs. 11.6% untreated, P < 0.05). Combined treatment with imatinib and ZME upregulated the expression of Bax (5-fold in K562, 3-fold in U266) and P-TEN (2-fold in K562, 2.8-fold in U266) genes and downregulated the expression of Bcl-2 (0.3-fold in K562, 0.3-fold in U266), BCR-ABL (0.5-fold in K562), and c-MYC (0.4-fold in K562, 0.2-fold in U266) genes (P < 0.05). Molecular docking showed strong binding affinities between ZME constituents (carvacrol and thymol) and BCL-2 and ABL proteins.

Conclusions

ZME shows potential as a complementary agent in vitro, warranting further investigation.